This invention is concerned with a new class of appetite stimulants--(9-carboxy-11H-pyrrolo[2,1-b] [3]benzazepin-11-ylidene) piperidines.
The compounds 3-carboxycyproheptadine and its 10,11-dihydro analog are known to have appetite stimulant properties. Also, the heterotricyclic pyrrolo[2,1-b] [3]benzazepine is known. Now with this invention there is described a series of (carboxy-pyrrolo[2,1-b] [3]benzazepine-11-ylidene) piperidines as potential appetite stimulants. However, studies of the carboxy derivatives of this series including 1-methyl-4-(9-carboxy-11H-pyrrolo [2,1-b] [3]benzazepine-11-ylidene) piperidine, 1-methyl-4-(2-carboxy-6, 11-dihydro-5H-pyrrolo[2,1-b] [3]benzazepin-11-ylidene) piperidine, 1-methyl-4-(9-carboxy-6,11-dihydro-5H-pyrrolo[2,1-b] [3]benzazepin-11-ylidene) piperidine, and 1-methyl-4-(2-carboxy-11H-pyrrolo [2,1-b] [3]benzazepin-11-ylidene) piperidine have led to the unexpected result that only the 9-carboxy derivatives of a 5,6-unsaturated analog are active. Therefore, it is an object of this invention to provide certain novel (9-carboxy-11 H-pyrrolo[2,1-b] [3]benzazepine-11-ylidene) piperidines, and their pharmaceutically acceptable salts as a new class of appetite stimulants. Other objects of this invention are:
(1) to provide a novel method of stimulating appetite with the new compounds; PA1 (2) to provide the novel pharmaceutical formulations comprising the new compounds; and PA1 (3) to provide novel processes for preparing these new compounds. PA1 R.sup.1 is hydrogen, carboxy, lower alkyl especially C.sub.1-6 alkyl such as methyl, propyl, or hexyl; and PA1 R is lower alkyl especially C.sub.1-6 alkyl or lower (cycloalkylalkyl) especially C.sub.3-6 cycloalkyl C.sub.1-3 alkyl such as cyclopropyl-methyl, cyclopentylethyl or the like. PA1 (1) the acid addition salts of the amino functions obtained via treatment of the compounds with a non-toxic acid such as hydrochloric, sulfuric, phosphoric, citric, tartaric, succinic, or the like; PA1 R.sup.3 is cyano or lower alkyl carboxylic ester; and PA1 R is lower alkyl or lower (cycloalkylalkyl). PA1 R.sub..alpha..sup.3 is halo; and PA1 R is lower alkyl or lower (cycloalkylalkyl), with cuprous cyanide in an aprotic solvent such as N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoramide or diethylene glycol dimethyl ether preferably N,N-dimethylformamide at about 100.degree. to about 200.degree. C., preferably at 150.degree.-175.degree. C., until the reaction is substantially complete, usually for about 3 hrs. to about 20 hrs., preferably 4-6 hrs.